This proposal describes a research program that will develop new chromium carbene-based synthetic organic methodology and apply these techniques to the total syntheses of a variety of biologically active natural products. The new methods focus on cyclization reactions initiated from chromium carbene complexes and templated by chromium carbonyl fragments in order to effect rapid and efficient construction of target molecules with facile control of key regiochemical aspects. A significant number of new methodologies are proposed with supporting preliminary results. Specific synthetic target molecules include: the orthoquinone antitumor antibiotic aegyptinone A; the coronary artery dilator 1,2- dihydrotanshinquinone; the carbazole free radical scavengers carazostatin and antiostatin A4; a cytotoxic and antiviral indolocarbazole; rubiflavinone C-2, a component of the antitumor antibiotic mixture rubiflavin and a model for the anthracyclinone antibiotic A51493A; the antiinflammatory diterpene glycoside pseudopterosin G; the sesquiterpene antitumor antibiotic 6-deoxyilludin M; and the cytotoxic terpene faveline methyl ether. The organic chemistry objectives for this proposal include: demonstration of the utility of benzannulation reactions of dienyl chromium carbene complexes for the construction of ortho alkoxy phenols and the derived ortho quinones; efficient annulation of 4H-pyran-2-one rings upon 2-alkoxy phenols; demonstration of the ability of dienyl chromium carbene complexes to serve as general precursors of dienyl ketenes and thereby to cyclohexadienones, cycloheptadienones, 2- aminophenols, ortho quinone methides, pyridines, pyridones and pyrones; development of the thermal reactions of dienyl chromium carbene complexes which can lead to indenes, indenones, and 2-alkoxy aromatic amines; development of a firm mechanistic basis for each process; and demonstration of the value of these new synthetic methods to organic synthesis in general and to the syntheses of a number of medicinally active target compounds in particular.